title: Antitumor immune response of dendritic cells (DCs) expressing tumor-associated antigens derived from induced pluripotent stem cells: in comparison to bone marrow-derived DCs.
abstract: It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) is a serious problem in DC-based immunotherapy. Therefore, we used the induced pluripotent stem (iPS) cell-derived DCs (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of bone marrow-derived DCs (BMDCs), then the aforementioned problems may be solved. In our study, we induced iPSDCs from iPS cells and examined the capacity for maturation of iPSDCs compared to that of BMDCs in addition to the capacity for migration of iPSDCs to regional lymph nodes. We adenovirally transduced the hgp100 gene, natural tumor antigens, into DCs and immunized mice once with the genetically modified DCs. The cytotoxic activity of CD8 (+) cytotoxic T lymphocytes (CTLs) was assayed using a (51) Cr-release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. Our results showed that iPSDCs have an equal capacity to BMDCs in terms of maturation and migration. Furthermore, hgp100-specific CTLs were generated in mice immunized with genetically modified iPSDCs. These CTLs exhibited as high a level of cytotoxicity against B16 cells as BMDCs. Moreover, vaccination with the genetically modified iPSDCs achieved as high a level of therapeutic efficacy as vaccination with BMDCs. Our study clarified experimentally that genetically modified iPSDCs have an equal capacity to BMDCs in terms of tumor-associated antigen-specific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.
authors.affiliation: Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama, 641-8510, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Ojima
authors.forename: Keiji
authors.initials: K
authors.lastname: Hayata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Katsuda
authors.forename: Motoki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iida
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Mikihito
authors.initials: M
authors.lastname: Nakamori
authors.forename: Makoto
authors.initials: M
authors.lastname: Iwahashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004622:Embryo, Mammalian / Q000166:cytology / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000276:immunology* / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D058951:gp100 Melanoma Antigen / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D058951:gp100 Melanoma Antigen
keywords: DCs vaccine therapy; TAA-specific; antitumor immune response; genetically modified DCs; iPSDCs